[Natural Law]

The underlying statistical model implied is invalid because it presupposes that all mutations and variations have a negative consequence. This is like saying that chances of actually winning a lottery are the same whether you buy a ticket or not. While the vast majority of lottery tickets, like mutations, are losers there are and will continue to be winners. Evolution is the very rare occasion that a mutation is beneficial.

[mnehring]

The underlying statistical model implied is invalid because it presupposes that all mutations and variations have a negative consequence.

That's pretty much the flaw I read in this story. It is the assumption that a mutation only leads to a negative trait. For example, the mutation that causes sickle cell anemia also makes it where you can't get malaria so it would be a beneficial mutation in areas where malaria is prevalent. While sickle cell anemia is harmful, it isn't even as a fraction as deadly as malaria and could result in a stronger population in malaria prone areas.

[GodGunsGuts]

The author employs multiple statistical models, all of which point to the same thing—extinction. Tell me, now that we know genes are polyconstrained, and that a beneficial mutation for one gene will be harmful to many others, how is natural selection supposed to select for the beneficial mutation without fixing the harmful mutations as well?